Tyr-Pro-Trp-Gly-NH_2(Tyr-W-MIF-1)analogであるTyr-D-Pro-Trp-Gly-NH_2の抗侵害作用におけるμオピオイド受容体の関与について

We have previously reported that Tyr-D-Pro-Trp-Gly-NH_2 (D-Pro^2-Tyr-W-MIF-1) given spinally produces clearly a dose-dependent attenuation of the antinociception induced by Tyr-W-MIF-1 without affecting endomorphins- and[D-Ala^2, NMePhe^4, Gly(ol)^5]-enkephalin (DAMGO)-induced antinociception, and D-Pro^2-Tyr-W-MIF-1 at any doses used (0.025-1.2 nmol) does not show any antinociception or hyperalgesic effect by itself. In the present study, we found that D-Pro^2-Tyr-W-MIF-1 given supraspinally produced the antinociception, which is mediated by stimulation of μ-opioid receptors. D-Pro^2-Tyr-W-MIF-1 (0.5-16 nmol) given intracerebroventricularly (i.c.v.) produced an apparent dose-dependent antinociception. However, at the three highest doses (4, 8 or 16 nmol), there was a ceiling effect (about 30% MPE) where the increase in dose did not lead to a greater effect. The antinociception induced by D-Pro^2-Tyr-W-MIF-1 at a dose of 4 nmol was blocked by i.c.v. co-administration with the μ-opioid receptor antagonist D-Phe-Cys-Tyr-D-Trp-Orn-Thr-Pen-Thr-NH_2 (CTOP), but not by i.c.v. pretreatment with the μ_1-opioid receptor antagonist naloxonazine, the κ-opioid receptor antagonist, nor-binaltorphimine, or the δ-opioid receptor antagonist naltrindole. In contrast, the antinociception induced by DAMGO and Tyr-W-MIF-1 was blocked by i.c.v. co-administration with CTOP or by i.c.v. pretreatment with higher doses of naloxonazine, but not by pretreatment with nor-binaltorphimine or naltrindole. We propose that the antinociception induced by D-Pro^2-Tyr-W-MIF-1 and Tyr-W-MIF-1 is mediated by the stimulation of different subtypes of μ_2-opioid receptors

Influence of Varying Dietary Protein Levels on Glycation of Albumin, Tryptophan and Valine in the Plasma of Chickens

Glycation is a chemical reaction in which reducing sugars bind non-enzymatically to compounds containing amino groups. Avian species like chickens are hyperglycemic animals and have high body temperature compared to mammalian species, which enables avian species to accelerate the glycation of proteins and amino acids with glucose. Although varying dietary crude protein (CP) levels alter plasma concentrations of proteins and amino acids, the influence of varying CP levels on the glycation of plasma proteins and amino acids has not been studied so far. In the present study, therefore, glycation of albumin, tryptophan and valine in the plasma of chickens fed diets with varying CP levels (0, 10, 20, 40 and 60%) was examined. At the end of the experimental period, blood samples were collected and plasma concentrations of glycoalbumin, glycated tryptophan (tryptophan-Amadori product and (1R, 3S) - 1 - (D - gluco - 1, 2, 3, 4, 5 - pentahydroxypentyl) - 1, 2, 3, 4 - tetrahydro - β - carboline - 3 - carboxylic acid (PHP-THβC)), and valine-Amadori product were measured. Although plasma albumin concentration was reduced along with the decrease in dietary CP levels from 20% to 0%, glycoalbumin in the plasma was increased under such dietary conditions. Similar increase in the ratios of tryptophan-Amadori product to tryptophan and valine-Amadori product to valine in the plasma of chickens fed a protein-free diet was observed. These results suggest that dietary protein deficiency might enhance the non-enzymatic glycation of plasma proteins and amino acids in chickens

Dietary Supplementation with Lysine and Threonine Modulates the Performance and Plasma Metabolites of Broiler Chicken

Here, we investigated whether the optimal threonine (Thr) to lysine (Lys) ratio in high Lys diet improves the growth performance of modern broiler chickens at finisher period and determined the possible mechanism underlying improvement in the growth performance of chickens fed with high Lys or Lys + Thr diet using metabolome analyses. Eighteen 21-day-old chickens housed in individual cages were randomly divided into three groups of six chickens fed with different diets as follows: control diet, high Lys diet (150% Lys content of National Research Council requirement), and high Lys + Thr diet (0.68 of Thr/Lys in high Lys diet). Body weight gain (BWG) increased in chickens receiving high Lys diet as compared with those fed with the control diet (P<0.05); no significant difference was observed in BWG of chickens from high Lys + Thr and high Lys groups. Feed conversion ratio (FCR) was lower in chickens fed with high Lys or high Lys + Thr diet than in those on the control diet. Serotonin concentration increased in the plasma of chickens fed with high Lys diet as compared to those fed with other diets. A negative correlation was observed between plasma serotonin concentration and FCR. These results provide the first evidence on the use of high Lys in broiler diets to reduce FCR during finisher period, which may be associated with change in plasma serotonin concentration. These findings suggest that high Lys content in finisher diet, but not high Thr + Lys diet, may affect the peripheral serotonergic metabolism and improve FCR. Thus, plasma serotonin may serve as a biomarker of FCR in broilers

Glycated Tryptophan in the Plasma of Chickens Fed Tryptophan-excess Diets

When tryptophan is glycated with glucose, it results in forming two types of glycated tryptophan, glucose-tryptophan Amadori product and (1R, 3S)-1-(D- gluco-1,2,3,4,5-pentahydroxypentyl)-1,2,3,4-tetrahydro-β-carboline-3-carboxylic acid (PHP-THβC). Hyperglycemia and high body temperature in avian species are supposed to elevate the concentration of glycated tryptophan in the plasma of chickens fed tryptophan-excess diets. However, plasma concentrations of both glucose-tryptophan Amadori product and PHP-THβC have not been determined so far. Young chickens were fed tryptophan-excess diets (1, 2 or 3% excess) for 14 or 21 days, and plasma concentrations of two types of glycated tryptophan were measured using liquid chromatograph mass spectrometer (LC/MS). In the present study, we successfully detected and quantified both glucose-tryptophan Amadori product and PHP-THβC in the plasma, which revealed that plasma concentrations of glucose-tryptophan Amadori product and PHP-THβC were approximately 1 and 2-4μM, respectively. Furthermore, plasma concentrations of glycated tryptophan compounds significantly correlated to that of plasma tryptophans, and total amount of both glycated tryptophan compounds was almost 10% of plasma tryptophan